Macrosomia, prematurity, perinatal mortality, and congenital malformations are more common in infants of diabetic mothers than in infants of nondiabetic mothers. Offspring of diabetic women are also at an increased risk of developing obesity and glucose intolerance during childhood and young adulthood. The purposes of the project are to identify diabetes and impaired glucose tolerance during pregnancy in women in the Gila River Indian Community, to determine the effects of abnormal glucose tolerance on outcome of the pregnancy, and to determine long term prognosis for the women and their offspring. By means of a glucose tolerance test as well as chart review, the diabetes status of every woman is determined at two-yearly intervals and during the third trimester of each pregnancy. The characteristics of women who have diabetes or impaired glucose tolerance during the pregnancy are compared to those of women who are normal during the pregnancy and subsequently develop diabetes and to those of women who remain normal. These women and their offspring, after the age of 5 years, are followed at two yearly intervals and glucose tolerance tests are performed which include measurements of glucose and insulin. Offspring of diabetic women have more diabetes and more obesity than offspring of nondiabetic and prediabetic women. Fasting serum insulin concentrations were compared in nondiabetic offspring of nondiabetic, prediabetic, and diabetic women. Even after adjustment for fasting plasma glucose, the offspring of prediabetic and diabetic women had significantly higher insulin concentrations than offspring of nondiabetic women. In spite of the previously described effect of the intrauterine environment on the risk for obesity and diabetes, these data suggest that insulin resistance, as estimated by the fasting insulin concentration, is an inherited trait and is not induced simply by the exposure to the diabetic intrauterine environment.